Management of Preterm Labor

Berkman, ND, Thorp, JM Jr, Hartmann, KE, et al. Management of preterm labor. Evidence Report/Technology Assessment No. 18 (Prepared by Research Triangle Institute under Contract No. 290-97-0011). AHRQ Publication No. 01-E021. Rockville (MD) Agency for Healthcare Research and Quality. December 2000.

 

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Abstract

Objectives

Preterm labor is often a prelude to early births and the significant attendant burden of infant morbidity and mortality. To address the question of how best to manage women in preterm labor, the Research Triangle Institute-University of North Carolina Evidence-based Practice Center undertook a rigorous review of the scientific literature on: (1) appropriate criteria for diagnosing preterm labor and use of three biologic markers, fetal fibronectin (fFN), endovaginal ultrasound (EVUSD), and salivary estriol; (2) efficacy and effectiveness of tocolytics-pharmaceutical agents including beta-mimetics, calcium channel blockers, magnesium sulfate, nonsteroidal antiinflammatory disease drugs (NSAIDs), and ethanol that arrest preterm labor symptoms); (3) efficacy and effectiveness of antibiotics for treating covert infections that might have prompted preterm labor; and (4) efficacy of home uterine activity monitoring.

Search Strategy

We conducted a detailed search of the relevant literature using MEDLINE; EMBASE; the Cochrane Collaboration and its related York Database, International Pharmaceutical Abstracts; the Health Economic Evaluations Database; Genderwatch; and the Population Index. The Medical Subject Headings included premature labor, diagnosis, epidemiologic study characteristics, terms for specific therapies (biologic markers, antibiotics, and tocolytic agents) and costs, cost analysis, and cost-benefit analysis. We conducted an extensive search of the gray literature, chiefly government documents, with a focus on tocolytics and biologic markers.

Selection Criteria

Our inclusion criteria were randomized controlled trials (RCTs) and cohort or case-control studies on biologic markers, tocolytics, and antibiotics that met the following specifications: published from 1966 to 1999 in English, French, or German; including pregnant females of any age with signs and symptoms of preterm labor; involving inpatient and outpatient settings; and measuring delivery, maternal morbidities, and infant health outcomes. Home uterine activity monitoring was further restricted to RCTs published in English since 1980.

Data Collection and Analysis

We conducted dual and blinded reviews of abstracts of articles and pulled full articles. Those articles meeting inclusion criteria were given a detailed dual review and abstraction onto four (topic-specific) data extraction forms. We judged the quality of the individual articles (on internal validity, statistical considerations, clinical relevance of findings, an external validity) and the strength of the evidence overall in each topic area (considering consistency of findings over all studies, quality rating of each study, magnitude of important outcomes, and meta-analysis results). In addition to the systematic reviews of the literature, we conducted meta-analyses of treatment effects from first-line and maintenance tocolytics, antibiotics, and home uterine activity monitoring.

Main Results

The quality of this literature is questionable in many respects, including the definition of preterm labor, the size of the trials, confounding of results because of use of cointerventions, reliance on bivariate analyses without including stratified analyses such as would be available through survival analysis, and failure to separately analyze women who have conditions that culminate in medically indicated preterm births.

Both fFN and EVUSD present strong evidence of effectiveness from cohort studies as diagnostic tools for assessing the risk of preterm birth in women with preterm labor, mainly in terms of their negative predictive value. Both can identify women who are not likely to experience a preterm birth and thus help clinicians avoid unneeded therapy. The efficacy of these findings from RCTs is not yet available.

First-line treatment with certain tocolytics offers small improvements in pregnancy prolongation. Whether this prolongation is beneficial in improving neonatal outcomes has not been established. Tocolytics other than beta-mimetics offer greater efficacy at less risk; the benefits of beta-mimetics never exceeded other options, and their harms were potentially more severe than for other options. Ethanol is less efficacious than other tocolytic options and is an inappropriate treatment for women with preterm labor symptoms. In terms of gestational age at birth, prolongation of pregnancy, or birth weight, maintenance treatment with tocolytics conferred no benefits. Evidence of harms was high for beta-mimetics in relation to the probability of maternal risk (serious cardiovascular harms, minor cardiovascular harms, metabolic harms, and psychologic harms); harms for other tocolytics were regarded as low for maternal risk. All classes of tocolytics posed low short-term risk for fetal or neonatal outcomes. Long-term risk to the infant was not evaluated.

Therapy with antibiotics for occult in utero infections believed to be associated with preterm labor had mixed results, but meta-analysis indicated marginally significant improvements in two maternal outcomes (length of pregnancy and gestational age). Significant increases in birth weight were not found.

No RCT of home uterine activity monitoring that controlled for the cointervention of nursing support found a significant effect from use of this device. Meta-analysis confirmed this “no- effect” conclusion in relation to gestational age at birth and birth weight.

Conclusions

Based on the literature reviewed, two biologic markers (fFN and EVUSD) are found to be quite useful in identifying women in preterm labor who are at low risk of experiencing a preterm birth. Although the evidence remains mixed, certain tocolytics – beta-mimetics, calcium channel blockers, magnesium sulfate, and NSAIDs – appear effective in prolonging pregnancy when used as first-line agents in arresting preterm labor, but beta- mimetics in comparison with other tocolytics seem to present a higher risk of maternal harms. Ethanol is not found to be an appropriate tocolytic agent. Tocolytics are not useful as maintenance interventions. Antibiotics for suspected genital tract infections may be useful. Home uterine activity monitoring was found to confer no maternal or fetal/neonatal benefits.

The literature concerning the management of preterm labor is flawed in several ways relating largely to definitions of preterm labor, appropriate measures of outcomes, and use of survival analysis. Epidemiologic research as well as additional efficacy and effectiveness studies of the two biologic markers, selected tocolytics, and antibiotics are warranted.