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Genetic factors in preterm birth—the future

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Abstract:

The genetic regulation of common biological functions has redundant control mechanisms, and it is unlikely that a single marker will ever be identified that will be both highly sensitive and specific. It is more likely that combinations of gene and/or protein markers, perhaps also combined with obstetric family histories, will be required to achieve the goal of a truly sensitive and specific screening profile for spontaneous preterm labour and preterm birth. The rapidly evolving disciplines of genomics and proteomics are now beginning to be applied to the study of spontaneous preterm labour and preterm birth. These techniques are able to measure multiple markers (in the thousands) in a biological sample and, given the likely presence of biological changes that precede by weeks or even months the clinical manifestations of the disease, are ideally suited to the evaluation of spontaneous preterm labour and preterm birth. Over the next few years, these technologies will hasten a deeper understanding of the pathophysiology of spontaneous preterm labour, discover novel target molecules and diagnostic biomarkers and ultimately aid in formulating more effective interventions to prevent preterm birth. Pharmacogenomics is another rapidly evolving discipline that holds great promise for the treatment and prevention of spontaneous preterm labour and preterm birth. Because spontaneous preterm labour is a final common pathway for multiple aetiologies, there remains no reason why any single therapy will work optimally for all women. As patient-specific pharmacogenomic profiles are developed, it will be possible to develop patient-specific treatment regimens. Beyond that, it may become possible to identify those women who are, or are not, destined to labour spontaneously and give birth remote from term and to institute patient-specific preventive measures. Spontaneous preterm labour and preterm birth remains a syndrome, with a final common pathway for multiple aetiologies. As a result, no single explanation, marker or treatment is likely to be 100% sensitive, specific or successful. It is also clear, however, that there is a genetic predisposition in many cases of spontaneous preterm labour. Over the next few years, several recently developed diagnostic mechanisms, and others that have yet to evolve, will hold a greater potential than ever before to unlock the secrets of the genetic predisposition to spontaneous preterm labour and its underlying causes. An improved understanding of these mechanisms will allow clinicians to employ therapies that will be optimally effective for individual women and their unborn babies. Eventually, these advances could be applied to the presymptomatic prevention of spontaneous preterm labour. It is the intent of this manuscript to review the current status of these new technologies and disciplines and to speculate on their applications in the intermediate future.

Document Type: Research Article

DOI: https://doi.org/10.1111/j.1471-0528.2005.00595.x

Publication date: 2005-03-01

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