Oral nifedipine maintenance therapy after acute intravenous tocolysis in preterm labor

AIMS: Our aim was to evaluate the efficacy of maintenance oral nifedipine in pregnant women initially treated with intravenous ritodrine plus verapamil for preterm labor. METHODS: The study included 73 patients with preterm labor with intact membranes. Patients were randomized to receive either maintenance oral nifedipine therapy (n=37) administered 20 mg every six hours or no treatment (controls, n=36) after discontinuation of acute intravenous tocolysis. RESULTS: Compared to the control group, the mean +/- SD time gained from initiation of maintenance therapy to delivery (26.65 +/- 18.89 vs. 16.14 +/- 12.91 days, p=0.007) and the gestational age at delivery (37.03 +/- 2.06 vs. 35.1 +/- 3 weeks, p=0.003) were higher in the nifedipine maintenance therapy group. The proportion of patients who required one or more courses of subsequent intravenous therapy and perinatal outcomes were similar in the maintenance therapy and control groups. CONCLUSIONS: The gestational age and time gained from initiation of maintenance therapy to delivery were longer in women receiving oral maintenance tocolysis with nifedipine. However, maintenance therapy did not decrease the recurrence of preterm labor episodes or improve perinatal outcomes.     

Accuracy of fetal fibronectin to predict preterm birth in twin gestations with symptoms of labor

OBJECTIVE: To investigate accuracy of fetal fibronectin testing to predict preterm birth in twin gestations with symptoms of preterm labor. METHODS: We reviewed charts of all patients with twin gestations who underwent fetal fibronectin testing and presented with complaints of preterm labor between January 1, 2000, and June 30, 2004. We also reviewed the charts of all singleton gestations with similar complaints that had fetal fibronectin testing between January 1, 2000, and December 31, 2001. All samples were processed using a rapid fetal fibronectin detection system. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of fetal fibronectin testing in singleton and twin gestations in predicting delivery within 14 days of testing. RESULTS: Four hundred twenty-nine singletons and 87 twins met the inclusion criteria. The birth rate before 34 weeks of gestation for singletons was 3.5% compared with the rate of twin pregnancies of 28.7%. Fetal fibronectin predicted delivery within 14 days of testing with a sensitivity, specificity, and positive and negative predictive values in singleton gestations of 82%, 90%, 17%, and 99%, respectively. In twin gestations, fetal fibronectin predicted delivery within 14 days of testing with a sensitivity, specificity, and positive and negative predictive values of 71%, 74%, 19%, and 97%, respectively. CONCLUSION: As noted in singleton pregnancies, fetal fibronectin testing in twins has a high negative predictive value. Fetal fibronectin evaluation may be a useful tool in screening twins with symptoms of preterm labor, because a negative result places these women at a low risk for delivering within 2 weeks of testing.     

Clinical and cost-effectiveness of continuous subcutaneous terbutaline versus oral tocolytics for treatment of recurrent preterm labor in twin gestations.

OBJECTIVE: To compare the clinical and cost-effectiveness of treating recurrent preterm labor with continuous subcutaneous terbutaline versus oral tocolytics in twin gestations. STUDY DESIGN: In a retrospective, matched-cohort design, twin pregnancies treated as outpatients with continuous subcutaneous terbutaline were identified from a perinatal database, then matched 1:1 by gestational age at recurrent preterm labor to those receiving oral tocolytics. There were 353 patients per treatment group. A cost model was used to compare antepartum hospital, nursery, and outpatient charges. RESULTS: Infants of the subcutaneous terbutaline group had greater gestational age at delivery, higher birth weights, and less frequent neonatal intensive care unit admission. Charges for antepartum hospitalization and nursery were significantly less in the subcutaneous terbutaline group, while charges for outpatient services were less for the oral group. Mean total estimated charges were US$17,109 less for those receiving subcutaneous terbutaline. CONCLUSION: Improved clinical outcomes and decreased nursery utilization suggest cost-effectiveness of outpatient continuous subcutaneous terbutaline versus oral tocolytics for the treatment of recurrent preterm labor.     

Magnesium sulfate compared with nifedipine for acute tocolysis of preterm labor: a randomized controlled trial

OBJECTIVE: To compare the efficacy and side effects of intravenous magnesium to oral nifedipine for acute tocolysis of preterm labor. METHODS: A multicenter randomized trial was performed. Patients in active preterm labor who were at 24 to 33 weeks and 6 days of gestation were randomly assigned to receive magnesium sulfate or nifedipine. The primary outcome was arrest of preterm labor, defined as prevention of delivery for 48 hours with uterine quiescence. RESULTS: One hundred ninety-two patients were enrolled. More patients assigned to magnesium sulfate achieved the primary outcome (87% compared with 72%, P=.01). There were no differences in delivery within 48 hours (7.6% magnesium sulfate compared with 8.0% nifedipine, P=.92), gestational age at delivery (35.8 compared with 36.0 weeks, P=.61), birth before 37 and 32 weeks (57% compared with 57%, P=.97, and 11% compared with 8%, P=.39), and episodes of recurrent preterm labor. Mild and severe maternal adverse effects were significantly more frequent with magnesium sulfate. Birth weight, birth weight less than 2,500 g, and neonatal morbidities were similar between groups, but newborns in the magnesium sulfate group spent longer in the neonatal intensive care unit (8.8+/-17.7 compared with 4.2+/-8.2 days, P=.007). CONCLUSION: Patients who received magnesium sulfate achieved the primary outcome more frequently. However, delay of delivery, gestational age at delivery, and neonatal outcomes were similar between groups. Nifedipine was associated with fewer maternal adverse effects.     

Diltiazem for maintenance tocolysis of preterm labor: Comparison to nifedipine in a randomized trial

The objective of this study was to compare the safety and efficacy of maintenance tocolysis with oral diltiazem to oral nifedipine in achieving 37 weeks gestation. After successful intravenous tocolysis with magnesium sulfate, 69 women with preterm labor at > 35 weeks gestation were randomly assigned to nifedipine (20 mg orally every 4–6 hr), or diltiazem (30–60 mg orally every 4–6 hr). The primary outcome was the percentage of patients achieving 37 weeks gestation. Maternal cardiovascular alterations and neonatal outcomes were also assessed. Sixty-nine patients were available for final analysis. Less patients on diltiazem as compared to nifedipine achieved 37 weeks (15.1% vs. 41.7%, P = 0.019). Gestational age at delivery was also less for patients receiving diltiazem (35.5 × 3.5 weeks vs. 33.4 × 3.9 weeks, P = 0.022). There were fewer days gained in utero from randomization to delivery with diltiazem as compared to nifedipine; however, this difference was not statistically significant (22.4 × 16.3 days vs. 31.2 × 24.4 days, P = 0.084). Maternal blood pressure and pulse during tocolysis did not differ significantly between groups. Despite the theoretical advantages of diltiazem tocolysis, maintenance tocolysis with diltiazem offered no benefit over nifedipine in achieving 37 weeks gestation. The cardiovascular alterations with either drug in normotensive, pregnant patients appear minimal.     

Infection and labor. VI. Prevalence, microbiology, and clinical significance of intraamniotic infection in twin gestations with preterm labor

The purpose of this study was to establish the prevalence, microbiology, and outcome of microbial invasion of the amniotic cavity in twin gestation presenting with preterm labor and intact membranes. Amniocenteses were performed on both sacs of 46 women with twin gestations, preterm labor, and intact membranes. Indigo carmine was injected to ensure sampling of both amniotic sacs. Amniotic fluid was cultured for aerobic and anaerobic bacteria, Mycoplasma hominis, and Ureaplasma urealyticum. A positive amniotic fluid culture of at least one sac was noted in 10.8% (5/46) of patients admitted in preterm labor and in 11.9% (5/42) of women delivered of preterm neonates. Of the five patients with microbial invasion of the amniotic cavity, three had microorganisms isolated from both sacs. The presenting sac was involved in all cases, supporting an ascending route for microbial invasion of the amniotic cavity in twin gestation. Polymicrobial infection was found in three of the eight amniotic sacs with positive cultures. In two cases different organisms were isolated from each sac. All patients with positive amniotic fluid cultures were delivered of preterm infants within 48 hours of amniocentesis. Patients with positive amniotic fluid cultures presented with preterm labor at an earlier gestational age and with more advanced cervical dilatation than did women with negative amniotic fluid cultures. Clinical evidence of chorioamnionitis subsequently developed in two of five women with positive amniotic fluid cultures. The interval between amniocentesis and delivery was shorter in women with positive amniotic fluid cultures than in women with negative amniotic fluid cultures (median: 3.5 vs 168 hours, p less than 0.0001). Infants born to women with microbial invasion of the amniotic cavity had a lower median birth weight and a higher incidence of respiratory distress syndrome than those born to women with negative amniotic fluid cultures (birth weight: 1085 vs 1975 gm, p = 0.024; respiratory distress syndrome: 37.5% vs 8.3%, p = 0.04).     

Prediction and prevention of spontaneous preterm birth in twin gestations

The incidence of twin gestation has increased significantly over the past 30 years. One of the most significant public health implications of this trend is the increased incidence of preterm birth (PTB). Efforts to improve neonatal outcomes must address the rate of PTB, particularly among multiple gestations, which contribute a disproportionate share to the burden of PTB and neonatal morbidity. There is evidence that sonographic cervical length assessment and fetal fibronectin testing can identify twin pregnancies at risk for PTB, but, to date, there are no proven interventions for prevention of PTB in this population. Perhaps the most promising is vaginal progesterone, which has been shown to reduce the risk of PTB in a cohort of women that included twin gestations. However, the study lacked statistical power to definitively answer this question. Identification of an appropriate treatment for twin gestations recognized to be at increased risk for prematurity will help to decrease overall rate of PTB, a significant public health problem in the United States.     

Efficacy of aggressive tocolysis for preterm labor with advanced cervical dilatation

Objective.?Study the effectiveness of tocolysis for preterm labor with advanced cervical dilatation (???3?cm) to achieve sufficient latency for the effect of steroids to occur, and delivery of more mature neonates.

Study design.?We studied 249 singleton pregnancies, 23–36 weeks gestation in preterm labor, stratified by weeks of gestation and degree of cervical dilatation (Group A: 117, <?3?cm; Group B: 132, ???3?cm) who were given tocolysis and compared for the length of latency and neonatal outcome.

Results.?Maternal characteristics were similar between groups except African-American women were admitted with more advanced cervical dilatation. Latency ??72?hours was achieved in Group A: >?75% at all gestational ages, and Group B: >?50%. Latency >?72?hours, according to the degree of cervical dilatation, was for Group A: 90%, for Group B: 50–75% from >?3–5?cm dilatation, and 40% at 5.1–6?cm dilatation. Neonatal morbidity was mild with a decreased risk of long-term disability.

Conclusions.?Aggressive tocolytic therapy for preterm labor with advanced cervical dilatation is efficacious, allows for steroid therapy, and allows delivery of more mature neonates.     

The use of magnesium sulfate for tocolysis in preterm labor complicated by twin gestation and betamimetic-induced pulmonary edema

Maternal cardiorespiratory compromise has been reported to occur during the treatment of preterm labor with tocolytic agents. The risk for these complications is increased by the following factors: multiple gestation, the combination of magnesium sulfate and beta-adrenergic agonist, and the use of adrenocortico-steroids to hasten fetal pulmonary maturity. A case is presented of labor at 28 weeks' gestation complicated by pulmonary edema associated with the three risk factors listed above. The beta-agonist was discontinued with resolution of pulmonary edema. Intravenous magnesium sulfate was continued for 11 days. When uterine contractions finally overcame the tocolysis, delivery occurred. It appeared that uterine quiescence was achieved through the continued use of magnesium sulfate despite pulmonary edema in this case. The risk of continued tocolysis seemed to be counterbalanced by the benefits of prolonged intra-uterine existence for the fetuses.     

Adjunctive use of magnesium sulfate with ritodrine for preterm labor tocolysis

The purpose of the study was to determine if the adjunctive administration of magnesium sulfate with ritodrine would result in decreased dosage requirements of ritodrine, and, therefore, decrease the incidence of ritodrine-associated side effects. Candidates for tocolysis were prospectively randomized so that some received a uniform tocolytic dose of magnesium sulfate in a blinded protocol. All patients received a ritodrine infusion which was titrated in the standard manner to achieve cessation of labor. Evaluations included interval cumulative ritodrine dose, maximal ritodrine infusion rate, fluid balance, and blood chemistry studies. Contrary to our hypothesis, there were significantly more cardiovascular effects in the group that received ritodrine plus magnesium sulfate (11/24) than in the group that received ritodrine alone (1/17) (p less than or equal to 0.02). The predominant side effect was chest pain, frequently associated with electrocardiogram changes indicative of myocardial ischemia. These results are consistent with the current understanding of the regulatory mechanisms of these tocolytic agents. We conclude from the results of our prospective, randomized, blinded study that the adjunctive use of magnesium sulfate with ritodrine is associated with an unacceptable increase in serious side effects and probably does not improve efficacy.     

Is misoprostol safe for labor induction in twin gestations?

OBJECTIVE: To compare the safety and efficacy of intravaginal misoprostol to oxytocin for the induction of labor in twin gestations. METHODS: All twin gestations that underwent induction of labor with misoprostol or oxytocin during a 4-year period were identified from the Mount Sinai obstetrical database. Only twins > or = 34 weeks with a vertex presenting twin A were included. Labor and delivery characteristics, maternal complications and neonatal outcomes were compared between the two groups. RESULTS: Of 134 patients with twins, 57 initially received misoprostol and 77 received oxytocin. These groups had similar demographics, but women who received misoprostol had less cervical dilation (0.8 vs. 2.2 cm, p < 0.0001) and were less likely to be multiparous (19% vs. 44%, p = 0.003). There was a shorter length of induction to delivery (7.8 hours vs. 15.1 hours, p = 0.001) and a trend toward a lower cesarean section rate (16.9% vs. 31.6%, p = 0.06) in the oxytocin-only group. There were no cases of uterine rupture or maternal mortality in this series. There were no significant differences in neonatal outcomes between the two groups, but the sample size was underpowered to detect significant differences between the groups. CONCLUSIONS: Misoprostol and oxytocin both appear to be safe and efficacious for use in inductions of labor in twins in this limited retrospective investigation. The safety of these agents with regard to neonatal outcomes should be confirmed by larger studies.     

Maintenance tocolysis with oral micronized progesterone for prevention of preterm birth after arrested preterm labor

Objective

To evaluate the efficacy of maintenance therapy with oral micronized progesterone (OMP) for prolongation of pregnancy in cases of arrested preterm labor.

Methods

Ninety women at 24–34 weeks of singleton pregnancy with intact membranes and arrested preterm labor were randomly allocated to receive OMP (n = 45) or placebo (n = 45) daily until 37 weeks or delivery, whichever was earlier. Outcome parameters were compared using Student t test, χ² test, Fisher exact test, and log-rank χ² test.

Results

OMP significantly prolonged the latency period (33.29 ± 22.16 vs 23.07 ± 15.42 days; P = 0.013). Log-rank analysis revealed a significant difference in mean time to delivery between the 2 groups (P = 0.014). There were significantly fewer preterm births (33% vs 58%; P = 0.034) and low birth weight neonates (37% vs 64%; P = 0.017), and significantly higher mean birth weight (2.44 ± 0.58 vs 2.14 ± 0.47 kg; P = 0.009) in the OMP group. Perinatal outcomes and adverse effects were similar in the 2 groups.

Conclusion

Maintenance tocolysis with OMP significantly prolonged pregnancy and decreased the number of preterm births.Clinical Trial Registry of India: CTRI/2011/10/002043.     

Efficacy of aggressive tocolysis for preterm labor with advanced cervical dilatation.

OBJECTIVE: Study the effectiveness of tocolysis for preterm labor with advanced cervical dilatation ( > or = 3 cm) to achieve sufficient latency for the effect of steroids to occur, and delivery of more mature neonates. STUDY DESIGN: We studied 249 singleton pregnancies, 23-36 weeks gestation in preterm labor, stratified by weeks of gestation and degree of cervical dilatation (Group A: 117, < 3 cm; Group B: 132, 3 cm) who were given tocolysis and compared for the length of latency and neonatal outcome. RESULTS: Maternal characteristics were similar between groups except African-American women were admitted with more advanced cervical dilatation. Latency 72 hours was achieved in Group A: > 75% at all gestational ages, and Group B: > 50%. Latency > or = 72 hours, according to the degree of cervical dilatation, was for Group A: 90%, for Group B: 50-75% from > 3-5 cm dilatation, and 40% at 5.1-6 cm dilatation. Neonatal morbidity was mild with a decreased risk of long-term disability. CONCLUSIONS: Aggressive tocolytic therapy for preterm labor with advanced cervical dilatation is efficacious, allows for steroid therapy, and allows delivery of more mature neonates.     

Contributions of ischaemic placental disease to preterm birth in twin gestations

Objective.?To evaluate the extent to which ischaemic placental disease (IPD) – defined as women or newborns diagnosed with pre-eclampsia, small for gestational age (SGA), or abruption, is associated with preterm birth in twin gestations.

Methods.?A population-based study of women who delivered twin live births and stillbirths at 20–44 weeks gestation from 1995–2004 in the US was performed (n?=?1,105,666). We compared the frequency of IPD in term and preterm (<37 weeks) twin births. SGA was defined as twins with birthweight <10th percentile for gestational age, and corrected for infant sex. The association between IPD and preterm birth was expressed as hazard ratio, derived from Cox proportional hazard regression models after adjusting for potential confounders.

Results.?The overall rate of twin preterm birth was 57%. IPD was present in 20% of twin preterm births in comparison to a rate of 16% at term. Both pre-eclampsia and abruption, but not SGA, were associated with increased preterm birth rates. Women with two or more of the IPD conditions were more likely to deliver at preterm than at term gestations.

Conclusion.?In comparison to twin births delivered at term, IPD is more common in preterm births. Efforts to understand the role of IPD in twin gestations based on preterm birth subtypes may reveal important insights.     

Case series of labor induction in twin gestations with an Intrauterine Balloon catheter.

The efficacy and safety of labor induction using an intrauterine balloon catheter in twin pregnancies has been evaluated. During the study period (1992-1997), labor was induced at 36-42 weeks in 17 twin gestations. Labor induction was indicated for preeclampsia (n = 10), birth weight discordance (n = 3), suspected fetal distress (n = 2) and postdates (n = 2). Twin A was in vertex presentation in all cases. An intrauterine balloon catheter was inserted transcervically followed by augmentation whenever required. Vaginal delivery was achieved in 15 (88.2%) patients. The mean interval from balloon insertion to delivery was 17.05 h, with 80% deliveries occurring within 24 h of catheter insertion and 80% occurring within 12 h of catheter expulsion. Birth weight was 2,514+/-244 and 2,421+/-367 g for twin A and B, respectively. Oxytocin was required in 4 patients. Postpartum hemorrhage was noted in 1 patient. One patient with no progress of labor and 1 with suspected intrapartum fetal distress required cesarean section. All neonates had a 5-min Apgar score of 10. The data suggest that an intrauterine balloon catheter appears to be safe and effective to induce labor in twin gestations.     

Abdominal electromyography may predict the response to tocolysis in preterm labor

Objective

To determine whether abdominal electromyography can predict the response to tocolysis in pregnant women in preterm labor.

Study design

This study was carried out at the Department of Obstetrics and Gynecology, Menofyia University Hospital in Egypt. Fifty pregnant women in preterm labor who fulfilled the inclusion criteria were enrolled. Baseline abdominal electromyography was performed. Tocolysis in the form of hexoprenaline sulphate infusion was started for all women and electromyography was repeated after 24 h in responders but only after 6 h in non responders. The receiver operating characteristics curve was drawn to calculate specificity of the electromyography at 100% sensitivity. Results were tabulated and statistically analyzed.

Results

Forty women responded to tocolysis by delaying delivery for more than 48 h. There was a significant reduction in the frequency of uterine contractions after tocolysis (3.76 ± 0.92 versus 2.32 ± 2.05 contractions per 10 min; P < 0.001). Similar significant reductions affected the duration and amplitude of uterine action potentials (25.08 ± 9.74 versus 14.4 ± 17.16 s; P < 0.001, 40.8 ±  25.89 versus 28.32 ± 29.38 mV; P < 0.001). At a sensitivity of 100% and using ROC curve, abdominal electromyography of amplitude of 82 mV lasting for 30 s or more had a specificity of 90%, positive and negative predictive values of 67% and 95%, and a diagnostic accuracy of 88% in predicting preterm labor.

Conclusion

Abdominal electromyography may predict the response to tocolysis in preterm labor.