The molecular mechanisms of term and preterm labor: Recent progress and clinical implications

Keelan, J.A., Coleman, M. and Mitchell, M.D. (1997) The molecular mechanisms of term and preterm labor: Recent progress and clinical implications. Clinical Obstetrics and Gynecology, 40 3: 460-478. doi:10.1097/00003081-199709000-00004


Author Keelan, J.A.
Coleman, M.
Mitchell, M.D.
Title The molecular mechanisms of term and preterm labor: Recent progress and clinical implications
Journal name Clinical Obstetrics and Gynecology   Check publisher's open access policy
ISSN 0009-9201
Publication date 1997-09
Sub-type Article (original research)
DOI 10.1097/00003081-199709000-00004
Volume 40
Issue 3
Start page 460
End page 478
Total pages 13
Place of publication New York, N.Y. U.S.A.
Publisher Harper & Row
Language eng
Subject 1103 Clinical Sciences
1115 Pharmacology and Pharmaceutical Sciences
Formatted abstract
Current tocolytic protocols rely largely on the use of β-mimetics to induce myometrial quiescence and delay delivery. Unfortunately, the rapid transplacental passage and poor receptor specificity of the commonly used β- mimetics results in widespread activation of intrauterine and extrauterine β1 and β2 receptors. The use of β-mimetics is associated with a range of well-recognized and potentially dangerous side effects for mother and fetus. The value of continued use of β-agonists after obtaining uterine quiescence also has been the subject of recent debate. In this article we have attempted to explore the biochemical and molecular rationale for the use of alternative therapeutic modalities in the treatment and prevention of PTL. In the light of the current view that the term 'preterm labor' covers a considerable diversity of causes, we propose that a range of treatment regimes should be chosen on the basis of the diagnosis and classification of the patient according to the their particular condition. Although the measurement of several biochemical parameters have been suggested to be of use in predicting PTL, we believe that a panel of diagnostic indicators (e.g., free or total CRH, IL-6, extracellular matrix proteases, fetal fibronectin) is more likely to provide useful diagnostic information on which appropriate treatment modalities can be selected Table 1). Because of the complex and interactive nature of the mechanisms operating within the intrauterine environment to regulate myometrial activation and uterotonin production, we speculate that a combination of tocolytics, anti-inflammatory agents, uterotonic antagonists, and receptor blockers is likely to be more effective than a monotherapeutic approach, which focuses on only one facet of the process of uterine activation for pharmacologic intervention. For example, the use of antibiotics, PGHS inhibitors, and/or β-mimetics might be an appropriate first line of treatment for infection-associated PTL in extreme prematurity. If it is successful, this treatment might be followed by longer term use of a progestagen and/or NO donor to maintain myometrial quiescence until closer to term. Alternatively, use of progesterone or oxytocin antagonists may be effective in augmenting the actions of β-mimetics while reducing their side effects, whereas other combinations may be useful as long-term prophylactics in women with a high risk of developing PTL. Improvements continue in our diagnostic ability to correctly identify the different causes of preterm labor. We anticipate that careful selection of differing combinations of therapeutic options will result in significant reductions in the morbidity, mortality, and healthcare costs associated with preterm birth.
Keyword Corticotropin-releasing Hormone
Normal Human-pregnancy
Human Fetal Membranes
Tumor-necrosis-factor
Amniotic-fluid
Human Myometrium
Binding Protein
Human Parturition
Rat Myometrium
Oxytocin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
 
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Created: Thu, 26 Aug 2010, 12:55:53 EST