Nifedipine versus fenoterol in the management of preterm labor: a randomized, multicenter clinical study.

PURPOSE: To compare the efficacy of nifedipine and fenoterol in the management of threatened preterm labor (TPL). METHODS: A randomized and multicenter study assessing the tocolytic effect of nifedipine versus fenoterol in patients admitted to the participating maternity units with a diagnosis of TPL and a cost-savings study for economic assessment. For a power of 80% and an α error equal to 0.05, 132 consecutive patients were recruited during the study period; 66 patients were assigned to each group. A χ(2) analysis and a mean differences test were performed according to variable types and survival curves per intention-to-treat. RESULTS: Demographics were similar in both groups. The latency period was similar in both groups (26.7 vs. 25.6; p = 0.3). There were no differences in the results obtained. Nifedipine failed more frequently to obtain tocolysis when used as a first-line agent (80 vs. 90%, p = 0.0001). The group treated with fenoterol showed more drug adverse events (57.8 vs. 19.0%, p = 0.0001). The economic assessment did not evidence a significant difference in terms of cost savings between groups treated with either drug. CONCLUSION: The present study failed to demonstrate either clinical or economic superiority of any of the two drugs used in TPL management. The highest failure percentage of nifedipine when used as a first-line agent should encourage further research.

Factors associated with tocolytic hospitalizations in Taiwan: evidence from a population-based and longitudinal study from 1997 to 2004.

BACKGROUND: The use of tocolytic hospitalization in antenatal care is controversial and worthy of more research. We investigated individual, institutional, and area factors that affect the use of tocolytic hospitalizations in Taiwan where fertility has rapidly declined. METHODS: Longitudinal data from the 1996 to 2004 National Health Insurance Research Database in Taiwan were used to identify tocolytic hospitalizations. The probit model was used to estimate factors associated with tocolytic hospitalizations. RESULTS: The decline in fertility was significantly associated with the probability of tocolytic hospitalizations. Several physician and institutional factors-including physician's age, hospital ownership, accreditation status, bed size, and teaching status-were also significantly correlated to the dependent variables. CONCLUSIONS: The provision of inpatient tocolysis is influenced not only by clinical considerations but also by physician, institutional, and area factors unrelated to clinical need. Fertility declines in Taiwan may have led obstetricians/gynecologists to provide more tocolysis to make up for their lost income. If the explanation is further validated, reimbursement policies may need to be reviewed to correct for overuse of inpatient tocolysis. The correlation could also be explained by the increasing use of artificial reproductive technologies and higher social value of newborns. In addition, the physician and institutional variations observed in the study indicate potential misuse of inpatient tocolysis that warrant further investigation.

Cost-effectiveness of fibronectin testing in a triage in women with threatened preterm labor: alleviation of pregnancy outcome by suspending tocolysis in early labor (APOSTEL-I trial).

BACKGROUND: At present, women with threatened preterm labor before 32 weeks of gestation are, after transfer to a perinatal center, treated with tocolytics and corticosteroids. Many of these women are treated unnecessarily. Fibronectin is an accurate predictor for the occurrence of preterm birth among women with threatened preterm labor. We will assess whether triage of these women with fibronectin testing, cervical length or their combination is cost-effective. METHODS/DESIGN: We will investigate a prospective cohort of women referred to a perinatal centre for spontaneous threatened preterm labor between 24 and 34 weeks with intact membranes. All women will be tested for fibronectin and cervical length. Women with a cervical length <10 mm and women with a cervical length between 10-30 mm in combination with a positive fibronectin test will be treated with tocolytics according to local protocol. Women with a cervical length between 10-30 mm in combination with a negative fibronectin test will be randomised between treatment with nifedipine (intervention) and placebo (control) for 48 hours. Women with a cervical length > 30 mm will be managed according to local protocol. Corticosteroids may be given to all women at the discretion of the attending physician. Primary outcome measure will be delivery within 7 days. Secondary outcome measures will be neonatal morbidity and mortality, complications of tocolytics, costs and health related quality of life. The analysis will be according to the intention to treat principle. We anticipate the probability on preterm birth within 7 days in the group of women with a negative fibronectine test to be 5%. Two groups of 110 women will be needed to assure that in case of non-inferiority the difference in the proportion of preterm deliveries < 7 days will be within a prespecified boundary of 7.5% (one sided test, beta 0.2, alpha 0.05). Data obtained from women with a positive and negative fibronectin tests in both the cohort study and the trial will be integrated in a cost-effectiveness analysis that will assess economic consequences of the use of fibronectin. DISCUSSION: This study will provide evidence for the use of fibronectin testing as safe and cost-effective method in a triage for threatened preterm labor. TRIAL REGISTRATION: Nederlands Trial Register (NTR) number 1857, http://www.trialregister.nl.

Pregnancy and economic outcomes in patients treated for recurrent preterm labor.

OBJECTIVE: To compare clinical and cost-effectiveness of treating recurrent preterm labor (RPTL) with oral nifedipine versus continuous subcutaneous terbutaline infusion (SQT). STUDY DESIGN: Women with singleton gestations prescribed nifedipine for tocolysis following first diagnosis of preterm labor were identified. Women hospitalized with RPTL at <34 weeks were matched by gestational age (GA) after resuming nifedipine (NIF group) with women prescribed SQT (SQT group) after stabilization. Healthcare utilization costs were modeled and compared. RESULTS: This study analyzed 142 matched pairs. GA at RPTL (matched variable) was 30.4+/-2.6 weeks. GA at delivery was earlier in the NIF group versus the SQT group (35.7+/-3.1 weeks versus 36.6+/-2.1 weeks, p=0.004). Overall, infants from the NIF group had lower birth weights and higher nursery days than infants from the SQT group. Healthcare utilization costs were greater in the NIF group versus the SQT group (37,040+/-47,518 US dollars versus 26,546+/-25,386 US dollars, p=0.014). CONCLUSION: Treating RPTL with SQT versus oral nifedipine resulted in a later GA at delivery, improved neonatal outcome, and increased cost-effectiveness.

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.

Cost-effectiveness of fetal lung maturity testing in preterm labor.

OBJECTIVE: To determine the marginal cost-effectiveness of two strategies for preventing respiratory distress syndrome (RDS) resulting from preterm birth: 1) tocolysis with beta-mimetic agonists and treatment with corticosteroids (TREATALL), and 2) amniocentesis and testing for fetal lung maturity, with treatment based on test results (TESTALL), compared with no treatment. METHODS: We used a Markov decision analytic model to estimate the outcomes of each strategy, from a hospital-based perspective. Probability variables were obtained from the literature, whereas cost variables came from the Beth Israel-Deaconess Medical Center. Sensitivity analysis was performed on all variables. RESULTS: The most cost-effective strategy varied with the probability of RDS. TREATALL was the most cost-effective strategy above a probability of 17% (before 34 weeks' gestation), TESTALL was most cost-effective from 17% to 2% (34-36 weeks), and it was most cost-effective to use no treatment at probabilities less than 2% (after 36 weeks). TREATALL and TESTALL were both cost-saving compared with no treatment at probabilities of RDS above 2%. TREATALL was more highly favored as the costs of RDS and preterm birth increased, whereas TESTALL was more favored as the specificity of the test and the cost of maternal hospitalization increased. CONCLUSION: Although testing for fetal lung maturity is useful in many clinical situations, the cost-effectiveness of such testing in the setting of idiopathic preterm labor from a tertiary medical center perspective depends primarily on the probability and costs of RDS and the costs of non-RDS-related morbidity. At our institution, such testing is cost-effective between 34 and 36 weeks' gestation.

Efficacy and safety of indomethacin versus ritodrine in the management of preterm labor: a randomized study.

One hundred six patients in preterm labor with intact amniotic membranes and gestational age less than or equal to 32 weeks were randomized to receive either ritodrine hydrochloride or a 48-hour course of indomethacin for tocolysis. The relative efficacy, maternal and neonatal safety, and costs were evaluated to determine which may be the more appropriate first-line pharmacologic agent used to manage preterm labor. Fifty-four patients and 52 patients were randomized to receive ritodrine hydrochloride or indomethacin, respectively. Ritodrine hydrochloride and indomethacin were equally effective in inhibiting uterine contractions and delaying delivery. Delivery was delayed for at least 48 hours in 83 and 94%, and for at least 7 days in 70 and 75% of patients receiving ritodrine or indomethacin, respectively. Tocolysis with indomethacin was associated with no maternal side effects, whereas tocolysis with ritodrine hydrochloride was associated with a 24% incidence of serious cardiovascular and metabolic adverse effects prompting discontinuation of the drug. There were no differences in outcome between the infants exposed to indomethacin versus ritodrine hydrochloride when delivered either remote from therapy or during therapy, except for a statistically higher serum glucose in the infants exposed to ritodrine hydrochloride when delivered during tocolytic therapy. There were no cases of premature closure of the ductus arteriosus or pulmonary hypertension. Tocolysis with indomethacin was 17 times less costly than tocolysis with ritodrine hydrochloride. For gestations less than or equal to 32 weeks complicated by preterm labor, indomethacin may be an appropriate alternative as a first-line tocolytic agent.