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Berkman ND, Thorp JM Jr, Hartmann KE, et al. Management of Preterm Labor. Rockville (MD): Agency for Healthcare Research and Quality (US); 2000 Dec. (Evidence Reports/Technology Assessments, No. 18.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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Management of Preterm Labor.

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5Conclusions

Introduction

We discuss below the overall conclusions and implications of our analysis combining information from the evidence tables and the results in Chapter 3 and the meta-analyses discussed in Chapter 4. We begin by presenting our system for grading the strength of the information on the efficacy or effectiveness of treatment or interventions and harms data. Subsequent sections present our findings on individual topic areas, corresponding to our key clinical questions concerning the management of preterm labor (in order by biologic markers, tocolytics, antibiotics, and home uterine activity monitoring). Within each key therapy section, we present our evaluative grade for that body of literature. Finally, we discuss concerns relating to the literature as a whole.

Grading the Evidence

Chapter 2 introduced the discussion of our grading system for the preterm labor literature. Our overall approach for assigning categorical grades or ratings takes into account the quality of individual articles as scored according to the scale described in Chapter 2 as well as the strength and consistency or homogeneity of the findings across studies regarding a specific topic. The grades are defined as indicated below; the first set concerns benefits and the second set, harms.

Benefits Data Grades

We assign four basic grades for benefits. The first three grades indicate that the quantity of data is sufficient to make a judgment and that the overall data are good, fair, or poor in terms of supporting the conclusion that the intervention (e.g., pharmaceutical agent or biologic marker) is better than an alternative intervention or placebo. The fourth grade indicates that the quantity and quality of data are insufficient to draw any conclusions, chiefly because of small sample sizes or poor methods in the studies reviewed. The specific category definitions are as follows:

Benefits Data Grades

Good (A):The data are sufficient for evaluating the quality and strength of the findings. The data are consistent and indicate that the key drug or intervention is superior to alternative treatment or placebo for treating women with preterm labor.
Fair (B):The data are sufficient for evaluating the quality and strength of the findings. The data indicate that inconsistencies exist in the findings about the key drug or intervention and alternative treatment or placebo for treating women with preterm labor.
Poor (C):The data are sufficient for evaluating the quality and strength of the findings. The data do not show that the key drug or intervention is superior to alternative treatment or placebo for treating women with preterm labor.
Incomplete evidence (I):The data are insufficient for assessing the quality of the key drug or intervention for treating women with preterm labor based on limited sample size or poor methodology.
The sources of information leading to these categories are the following:
Efficacy (1):Evidence obtained from at least one well-designed RCT.
Effectiveness (2):Evidence obtained from more than one well-designed cohort or case-control study.

Harms Data Grades

We assigned two categorical ratings to the overall harms data reported for tocolytics in Chapter 3, "low" or "high." The rating reflects our judgment of the probability of risk from the intervention in question. The specific category definitions are as follows:

Low probability of risk:

- The side effects of treatment with the specific tocolytic that we noted from our review of articles were short term and not life-threatening.

- Considering the body of evidence, the frequency of occurrence was not substantially different from the frequency for an alternative tocolytic treatment or no treatment.

"High" probability of risk:

- The side effects of treatment with the specific tocolytic that we noted from our review of articles were life-threatening.

- Considering the body of evidence, the frequency of occurrence was substantially different from the frequency for an alternative tocolytic treatment or no treatment.

Biologic Markers

The key question for this topic was: What are the appropriate criteria for diagnosis of preterm labor? Relatedly, how much positive or negative predictive value does the use of biologic markers add to clinical opinion in diagnosing preterm labor?

Overall, the evidence-based review demonstrated that the two biologic markers studied- fFN and EVUSD-present strong evidence of effectiveness as diagnostic tools for assessing the risk of preterm birth in women with symptoms of preterm labor. Because of the lack of RCTs for biologic markers, we could not evaluate the efficacy of this intervention. Based on the relatively high quality and consistency of the data obtained from well-designed cohort studies, we assigned a quality grade for biologic markers evidence of Good (A-2).

Both tests were only moderately successful in predicting which women with a positive test would deliver before term, but they consistently exhibited strong NPVs, identifying women at low risk of preterm birth. Our conclusions are supported by the construction of contingency tables, allowing us to aggregate test performance information taken from individual articles. The outcome of this exercise (on fFN, as reported in Figure 9 and on EVUSD, as reported in Figure 10, Chapter 3) bolsters our qualitative finding that fFN exhibits a strong NPV.

Overall, our conclusion is that these biologic markers are untested as a means of assisting clinicians in improving outcomes in patients presenting with preterm labor. The evidence does indicate, however, that they offer valuable information that could allow women to avoid unnecessary treatments. In response to our key question, the literature supports the notion that these tests can usefully supplement clinical judgment, especially in terms of identifying women who are not likely to experience a preterm birth.

Tocolytics

The key question for this topic was: What is the efficacy and/or effectiveness of tocolytics in managing preterm labor?

We divided our analysis into two subtopics, one concerning first-line tocolytics and the other concerning maintenance therapy for a woman who has experienced an episode of preterm labor.

First-Line Tocolytic Therapy

The largest body of literature examined for this review concerned treatment with tocolytic agents for acute episodes of preterm labor: The tocolytics discussed included beta-mimetics, calcium channel blockers, magnesium sulfate, NSAIDs, and ethanol. We included both efficacy and effectiveness studies; research compared treatment with a particular class of tocolytic with a control group as well as with a different class of tocolytic drug. Overall, we assigned a quality grade to the first-line tocolytic literature of Fair (B-1), having determined that the data were sufficient for evaluating the quality of the findings and that the evidence comes from at least one well-designed RCT.

Literature comparing an intervention group of women receiving first-line treatment with tocolytics relative to a control group were available only for beta-mimetics, magnesium sulfate, and ethanol. Results were mixed: Some evidence of efficacy was shown in terms of estimated gestational age at delivery and prolongation of pregnancy with beta-mimetic or magnesium sulfate treatment. Only one beta-mimetic study 136 found a relationship between treatment and improved infant outcomes, showing significantly higher birth weight in the treatment arm. Data from the ethanol study 144 were insufficient to evaluate efficacy.

The largest body of literature reviewed compared the outcomes of treating women with beta-mimetics with the outcomes of treatment with other classes of tocolytics. Results again were mixed: Beta-mimetics were shown to have efficacy only relative to ethanol treatment in relation to prolonging pregnancy. 148 Other RCTs showed that all other classes of tocolytics had greater or not significantly different effects relative to beta-mimetics on birth outcomes. We also found mixed results for infant outcomes, but no study reported that beta-mimetics were a superior treatment. No other differences in efficacy were found between classes of tocolytics, and data from observational studies did not contradict the results of the RCTs.

Supplementing our qualitative review, some of the RCT data available from the individual studies were combined using meta-analytic techniques (Chapter 4). This methodology allowed us to compare all classes of tocolytics (i.e., beta-mimetics, calcium channel blockers, magnesium sulfate, NSAIDs) with a no-treatment group. The data suggest that all tocolytics, with the exception of ethanol, were effective in extending births to term (at or beyond 36 to 38 weeks gestation) compared with results in a no-treatment group. Evidence shows that there may be effect differences among beta-mimetics, calcium channel blockers, and magnesium sulfate; but more studies are needed for conclusive findings.

In sum, although inconsistencies exist in these data, overall the evidence supports the notion that treatment offers small improvements in pregnancy prolongation. If necessary, this may provide adequate time for administering corticosteroids for fetal lung development. Sufficient data were not available to determine directly whether this treatment has a directly beneficial effect on neonatal morbidity and mortality. Data concerning relative efficacy between drug classes are generally inconclusive, but they clearly support the conclusion that ethanol is less efficacious than other tocolytic options.

Maintenance Tocolytic Therapy

With the exception of one small study, 172 the efficacy studies of maintenance tocolytic literature showed no difference between treatment and control arms in managing women who had recently experienced an episode of preterm labor. These results were confirmed through our meta-analytic synthesis of results (Chapter 4 ). In terms of gestational age at birth, prolongation of pregnancy, or birth weight, no benefits from maintenance treatment were uncovered.

We graded this literature as Poor (C-1) in terms of showing efficacy or effectiveness of maintenance tocolytics. The data were sufficient for evaluating the quality of the literature, and no evidence supported the use of this therapeutic modality relative to no treatment.

Potential Harms From Tocolytic Therapy

The harms analysis examined tocolytic treatments for different classes of pharmaceuticals, but we did not distinguish between first-line and maintenance therapies. We assessed adverse events for both the mother and the fetus or neonate.

We graded beta-mimetics as "high" in probability of maternal risk. These drugs were shown to pose a risk to the mother of serious cardiovascular harms, minor cardiovascular harms, metabolic harms, and psychologic harms. In comparison, all other classes of tocolytic treatments were graded as "low" in relation to maternal risk. Significant levels of serious maternal complications were not shown.

We graded all classes of tocolytics as "low" risk in relation to fetal or neonatal harms. Evidence of short-term harms was inconsistent, and evidence to evaluate longer term problems was insufficient.

Additional Comments Concerning Tocolytic Therapy

The evidence from our analysis supports the generally held clinical belief that ethanol is an inappropriate treatment for women with preterm labor symptoms. Other treatments offer greater efficacy at less risk. Similar concerns would seem to be warranted with regard to treatment with beta-mimetics. Although this judgment may be an artifact of the relative wealth of data on this class of tocolytics relative to others, the benefits of beta-mimetics were never found to exceed other options, and the harms were shown to be potentially more severe.

Antibiotics

The key question for this topic was: What is the efficacy and/or effectiveness of antibiotics in managing preterm labor?

Results of our review concerning the efficacy of antibiotics for treating women with preterm labor were mixed. We graded this literature as Fair (B-1) on the basis of judgments that the data were sufficient for evaluating quality and that results from individual studies were mixed, although the meta-analysis found small, yet significant effects.

Two RCTs found improvements in all three delivery outcomes of interest: prolongation of pregnancy, mean gestational age at birth, and birth at a particular number of weeks. 191 , 192 In contrast, all other RCTs showed mixed results or no significant difference from placebo treatment. Results from survival analyses included in three RCTs were also mixed.

Our meta-analysis on six of these studies (Chapter 4) found a marginally significant increase in length of pregnancy of about 6 days. The data from nine studies combined to evaluate change in gestational age with antibiotic treatment also found a marginally significant increase of about 0.60 of a week. In contrast, no statistically significant increase in birth weight was found in the treatment relative to the control group; however, this may be an artifact of lack of power because of the small number of studies available for analysis.

Home Uterine Activity Monitoring

The key question for this topic was: What is the efficacy of home uterine activity monitoring in decreasing adverse maternal and neonatal outcomes in women who have experienced an episode of preterm labor in the current pregnancy?

The efficacy literature on home uterine activity monitoring in the treatment of women with preterm labor comprised only four studies. We give this literature a grade of Poor (C-1) because we judged that the information was sufficient for evaluating the quality of the findings. Also, we found that the evidence does not support the use of this therapeutic modality relative to using no treatment.

Three RCTs found no significant effect from home uterine activity monitoring. Our meta-analysis (Chapter 4) confirmed these conclusions in relation to gestational age at delivery and birth weight; however, meta-analysis results should be viewed with caution as they are based on data from only three studies. The fourth RCT in our analysis reported that home uterine activity monitoring significantly prolonged delivery to 37 weeks; 206 however, this research used an expanded definition of home uterine activity monitoring that included nursing support. The authors did not disentangle the two interventions, and so it is unclear whether the outcome improvement was related to the device or the nursing support. Overall, the preponderance of the evidence points to a lack of efficacy from home uterine activity monitoring in women with preterm labor. We concluded that additional research comparing use of the intervention with a control group and confirming these results in relation to this particular patient group is not needed.

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